bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022‒03‒20
nine papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

  1. J Immunol Res. 2022 ;2022 9595704
      Tumors of the gastrointestinal tract are one of the highest incidences of morbidity and mortality in humans. Recently, a growing number of researchers have indicated that nerve fibers and nerve signals participate in tumorigenesis. The current overarching view based on the responses to therapy revealed that tumors are partly promoted by the tumor microenvironment (TME), endogenous oncogenic factors, and complex systemic processes. Homeostasis of the neuroendocrine-immune axis (NEI axis) maintains a healthy in vivo environment in humans, and dysfunction of the axis contributes to various cancers, including the digestive tract. Interestingly, nerves might promote tumor development via multiple mechanisms, including perineural invasion (PNI), central level regulation, NEI axis effect, and neurotransmitter induction. This review focuses on the association between digestive tumors and nerve regulation, including PNI, the NEI axis, stress, and neurotransmitters, as well as on the potential clinical application of neurotherapy, aiming to provide a new perspective on the management of digestive cancers.
  2. Front Oncol. 2022 ;12 800499
      Background: Bibliometric analysis is used to gain a systematic understanding of developments in the correlation between neurotransmitters and tumor progression in research hotspots over the past 20 years.Methods: Relevant publications from the Web of Science Core Collection (WoSCC) were downloaded on August 1, 2021. Acquired data were then analyzed using the Online Analysis Platform of Literature Metrology ( and the CiteSpace software to analyze and predict trends and hot spots in this field.
    Results: A total of 1310 publications on neurotransmitters and tumor progression were identified, and 1285 qualified records were included in the final analysis. The country leading the research was the United States of America. The University of Buenos Aires featured the highest number of publications among all institutions. Co-citation cluster labels revealed the characteristics of 10 main clusters: beta-adrenergic receptors (β-AR), glutamate, neurotransmitters, serotonin, drd2, histamine, glycine, interleukin-2, neurokinin receptor-1, and nicotinic acetylcholine receptors (AchRs). Keywords and references burst detection indicated that apart from β-AR, dopamine receptor and cancer types like gastric cancer and glioblastoma are the newly emerging research hotspots.
    Conclusions: This study analyzed 1285 publications and 39677 references covering the topic of neurotransmitters and tumor progression and showed that while β-AR has always been a hot topic in this field, dopamine receptor is an emerging target for this research field, and gastric cancer and glioblastoma are the top two tumors that have garnered increasing attention and have become the focal point of recent studies.
    Keywords:  Citespace; anesthesia and tumor; bibliometric analysis; cancer; neurotransmitters
  3. Cancer Lett. 2022 Mar 10. pii: S0304-3835(22)00085-4. [Epub ahead of print] 215610
      Cancer neuroscience has emerged as a burgeoning field for the investigation of cancer-nervous system interactions. Perineural invasion (PNI) is defined as the presence of cancer cells that surround and/or invade the nerves infiltrating the tumor microenvironment. PNI is closely associated with increased tumor recurrence and diminished survival in many cancer types. Based on diverse in vitro, ex vivo, and in vivo models, mounting evidence suggests that the reciprocal crosstalk between nerves and cancer cells drives PNI, which is mediated by several factors including secreted neurotrophins, chemokines, exosomes, and inflammatory cells. Typical in vitro models using dorsal root ganglia (DRG) cells cocultured with cancer cells or other cell types allow the study of isolated factors. Ex vivo PNI models created by cocultivating cancer cells with explanted vagus and sciatic nerves enable the study of neuroaffinity in a time-saving and cost-efficient manner. In vivo models such as genetically engineered mouse models (GEMMs) and the chicken embryo chorioallantoic membrane (CAM)-DRG model, provide the nerve microenvironment needed to recapitulate the complex pathophysiological processes of PNI. Here, we summarize the current methods commonly used for modeling PNI and discuss the inherent pros and cons of these approaches for understanding PNI biology.
    Keywords:  Neural invasion; Neural remodeling; Neurogenesis; Neurotropism; Tumor innervation; Tumor neurobiology
  4. Acta Gastroenterol Belg. 2022 Jan-Mar;85(1):85(1): 35-45
      Background and study aims: The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer.Patients and methods: The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared.
    Results: Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups.
    Conclusion: While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.
    Keywords:  H. pylori; HER2; gastric cancer; neutrophil lymphocyte ratio; p53; platelet lymphocyte ratio
  5. Pathol Oncol Res. 2022 ;28 1610191
      Objective: The purpose of this study was to identify predictive factors for lymph node metastasis (LNM) in pT1 stage colorectal cancer (CRC) patients. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 2,697 consecutive pT1 stage patients who underwent surgical resection were retrospectively reviewed. Predictive factors for LNM were identified by the univariate and multivariate logistic regression analysis. The Kaplan-Meier curves and multivariate Cox regression analysis were used to evaluate the relationships between LNM and overall survival (OS) as well as cancer specific survival (CSS) of pT1 stage CRC patients. Results: The prevalence of LNM in pT1 stage CRC patients was 15.2% (410/2,697). Patient age <60 years (OR:1.869, 95% CI: 1.505-2.321, p < 0.001), poorly differentiated or mucinous or signet ring cell adenocarcinoma (OR:2.075, 95% CI: 1.584-2.717, p < 0.001), elevated carcinoembryonic antigen (CEA) level (OR:1.343, 95% CI: 1.022-1.763, p = 0.033) and perineural invasion (PNI) (OR:6.212, 95% CI: 3.502-11.017, p < 0.001) were significantly associated with LNM in pT1 stage patients. The survival analysis demonstrated that pT1 stage patients with LNM had a worse OS (5-year OS: 82.2% vs 88.7%, p = 0.020) and CSS (5-year CSS: 74.9% vs 81.5%, p = 0.041) than those without lymph node metastasis. Lymph node metastasis was an independent predictor of poor OS (HR: 1.543, 95% CI: 1.156-2.060, p = 0.003) and CSS (HR: 1.614, 95% CI: 1.121-2.324, p = 0.010) for pT1 stage colorectal cancer patients. Conclusion: Age, differentiation type, CEA level and perineural invasion were independent predictive factors for LNM in pT1 stage CRC patients. These findings might provide further risk stratification for pT1 stage patients and help clinicians identify high-risk individuals.
    Keywords:  SEER; colorectal cancer; lymph node metastasis; pT1 stage; predictive factors
  6. Sci Rep. 2022 Mar 14. 12(1): 4366
      Colorectal cancer remains a significant cause of morbidity and mortality, even despite curative treatment. A significant proportion of patients present emergently and have poorer outcomes compared to elective presentations, independent of TNM stage. In this systematic review and meta-analysis, differences between elective/emergency presentations of colorectal cancer were examined to determine which factors were associated with emergency presentation. A literature search was carried out from 1990 to 2018 comparing elective and emergency presentations of colon and/or rectal cancer. All reported clinicopathological variables were extracted from identified studies. Variables were analysed through either systematic review or, if appropriate, meta-analysis. This study identified multiple differences between elective and emergency presentations of colorectal cancer. On meta-analysis, emergency presentations were associated with more advanced tumour stage, both overall (OR 2.05) and T/N/M/ subclassification (OR 2.56/1.59/1.75), more: lymphovascular invasion (OR 1.76), vascular invasion (OR 1.92), perineural invasion (OR 1.89), and ASA (OR 1.83). Emergencies were more likely to be of ethnic minority (OR 1.58). There are multiple tumour/host factors that differ between elective and emergency presentations of colorectal cancer. Further work is required to determine which of these factors are independently associated with emergency presentation and subsequently which factors have the most significant effect on outcomes.
  7. Am J Dermatopathol. 2022 Apr 01. 44(4): 249-253
      BACKGROUND: Squamoid eccrine ductal carcinoma (SEDC) represents a subtype of eccrine carcinomas that are diagnostically challenging for both clinicians and dermatopathologists.OBJECTIVE: To provide an updated review of SEDC and examine patient outcomes with different treatment modalities.
    METHODS: A review of Ovid MEDLINE was performed to review the English language medical literature of SEDC.
    RESULTS: A comprehensive review of clinical presentation, histologic findings, rates of lymphovascular and metastatic disease, treatment modalities and recurrence rates are reviewed.
    LIMITATIONS: There is a limitation on available data because of the rare incidence.
    CONCLUSIONS: SEDC is a rare adnexal neoplasm with a relatively high rate of local recurrence, lymphovascular invasion, perineural invasion, and metastases. Clinicians should be aware of this entity as close follow-up is essential to detect recurrence and metastatic disease. Mohs micrographic surgery seems to result in superior patient outcomes.
  8. Clin Anat. 2022 Mar 15.
      In 1986, Rita Levi-Montalcini and Stanley Cohen were awarded with the Nobel Prize for Physiology and Medicine for the discovery of nerve growth factor. Among the experimental models used by Levi-Montalcini in the first part of her studies was the chick embryo chorioallantoic membrane, currently used in the study of tumor growth and angiogenesis. Levi-Montalcini grafted fragments of mouse sarcomas on to the chorioallantoic membranes of 4-6-day chick embryos and demonstrated that the tumors infiltrated the host blood vessels. Moreover, the ganglia showed hypertrophy, nerve fibers reaching to the implanted tumors. Levi-Montalcini hypothesized that the effect could have been mediated by a soluble factor, which was later identified as nerve growth factor. This article is protected by copyright. All rights reserved.
    Keywords:  Chorioallantoic membrane; Nerve growth factor; Tumor growth
  9. Front Oncol. 2022 ;12 759057
      Surgery remains the most effective cancer treatment, but residual disease in the form of scattered micro-metastases and tumor cells is usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. The much interesting intersection of anesthesiology and immunology has drawn increasing clinical interest, particularly, the existing concern of the possibility that the perioperative and intraoperative anesthetic care of the surgical oncology patient could meaningfully influence tumor recurrence. This paper examines current data, including recent large clinical trials to determine whether the current level of evidence warrants a change in practice. Available pieces of evidence from clinical studies are particularly limited, largely retrospective, smaller sample size, and often contradictory, causing several questions and providing few answers. Recent randomized controlled clinical trials, including the largest study (NCT00418457), report no difference in cancer recurrence between regional and general anesthesia after potentially curative surgery. Until further evidence strongly implicates anesthesia in future clinical trials, clinicians may continue to choose the optimum anesthetic-analgesic agents and techniques in consultation with their cancer patients, based on their expertise and current best practice.
    Keywords:  anesthesia; cancer; inhalational anesthetic; intravenous anesthetic; perioperative factors; tumor recurrence